Abstract
BackgroundCoronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation.MethodsThe follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19.ResultsBased on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019–30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081–5108.103)).ConclusionsFor the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.
Highlights
Iron deficiency anemia (IDA) and the anemia of chronic disease (ACD) are the two most common causes of anemia worldwide [1,2,3]
In COVID-19 patients an association between iron status and the risk of adverse outcomes has been reported showing that patients with low serum iron status and other indicators of iron deficiency anemia are likely to suffer from severe conditions in COVID-19 [4,5,6]
We addressed the question to which extend the classical biomarkers such as ferritin, soluble transferrin receptor, total iron-binding capacity, transferrin saturation, hepcidin, and serum iron can be used for the diagnosis of iron deficiency anemia, and zinc protoporphyrin (ZnPP) which is a less frequently used biomarker that, is less affected by the severity of inflammation compared to the others [14]
Summary
Iron deficiency anemia (IDA) and the anemia of chronic disease (ACD) are the two most common causes of anemia worldwide [1,2,3]. Anemia can be observed in up to 95% of critically ill patients even if their admission levels were in the normal range. Anemia is of clinical importance in critically ill patients because it is associated with morbidity and mortality. In COVID-19 patients an association between iron status and the risk of adverse outcomes has been reported showing that patients with low serum iron status and other indicators of iron deficiency anemia are likely to suffer from severe conditions in COVID-19 [4,5,6]. It is of concern to manage the anemia in critically ill patients to improve morbidity and mortality [3, 7, 8]. Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation
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